Influence of JY09 on Pharmacokinetics of Metformin , Rosuvastatin , and Digoxin and the QT Interval Study in Overweight Chinese Subjects

Beijing Dongfang Biotech

Status and phase: Completed; Phase 1

Conditions: Overweight; Diabetes Mellitus, Type 2

Treatments: Drug: Rosuvastatin calcium tablets; Drug: Metformin Hydrochloride tablet; Drug: Exendin-4 Fc fusion protein (JY09) injection; Drug: Digoxin tablet

Study type: Interventional

Funder types: Industry

Identifiers

NCT06247748

dfbt-jy09-ow-2023-101

Details and patient eligibility

About

This trial is conducted in china. The aim of the trial is as follows:

• To assess the effect of multiple subcutaneous injections of JY09 injection on the pharmacokinetic (PK) profile of multiple oral doses of metformin hydrochloride tablets, a single oral dose of Rosuvastatin calcium tablets, or digoxin tablets in overweight Chinese subjects;
• To assess the effect of multiple subcutaneous injections of JY09 injection on QT interval in overweight Chinese subjects.

Enrollment: 28 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Age: Overweight subjects with full capacity for civil behavior who are ≥ 18 years old and ≤ 45 years old (the ratio of the number of subjects of either sex is not less than 1/3).
2. Body weight: men ≥ 50.0 kg, women ≥ 45.0 kg, body mass index (BMI) ≥ 24.0 kg/m2 and ≤ 28.0 kg/m2 , BMI = weight (kg)/height (m2 ).
3. Those who do not plan to have children in the last 6 months, do not plan to donate sperm/eggs, and are willing to use effective contraception for 6 months after the end of dosing.
4. Fully understand the trial and possible adverse effects, have the ability to communicate normally with the investigator, as well as comply with study requirements, follow protocol procedures and limitations, and be able to visit on time.
5. Understand the content of the informed consent form, agree to participate in this trial and voluntarily sign the consent form.

Exclusion criteria

1. A clear history of central nervous system, cardiovascular system, renal, hepatic, pulmonary, metabolic, and musculoskeletal disorders or other notable diseases.
2. Individuals with gastrointestinal disorders, such as history of hepatobiliary disease, history of gastrointestinal disease, history of gastrointestinal surgery (except appendectomy) or history of chronic pancreatitis or idiopathic acute pancreatitis, and those with habitual diarrhea.
3. Previous tip-twisting ventricular tachycardia or other risk factors that can lead to malignant arrhythmias, or a family history of first-degree relatives (i.e., biological parents, siblings, or children) with short QT syndrome, long QT syndrome, unexplained sudden death, drowning, or sudden infant death syndrome in young adulthood (less than/equal to 40 years of age), or cardiac conduction block.
4. Have disorders of electrolyte metabolism such as hyperkalemia, hypokalemia, hypomagnesemia, hypomagnesemia, hypercalcemia or hypocalcemia.
5. If the results of vital signs (blood pressure, pulse, respiration, temperature) are abnormal and clinically significant, a retest is allowed to confirm the results if they are abnormal, and the abnormal values of each vital sign.
6. Physical examination, laboratory tests, 12-lead electrocardiogram (ECG), abdominal ultrasound, calcitonin and chest radiographs (orthopantomograms) suggesting the presence of abnormalities judged by the investigator to be clinically significant (retesting was allowed once).
7. Smokers who smoked an average of more than 5 cigarettes per day in the 3 months prior to screening or who could not give up smoking during their participation in the trial or who had a positive smoke test.
8. Those who have participated in other clinical trials as a subject within 3 months prior to screening.
9. Those who donated blood or blood products ≥400 mL within 3 months prior to screening.
10. Those who cannot tolerate venipuncture and have a history of needle and blood sickness.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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28 participants in 1 patient group

Exendin-4 Fc fusion protein (JY09) injection

Experimental group

Description:

D22 received a single subcutaneous abdominal injection of 1.2 mg of JY09 injection after completion of PK blood sampling; D29 to D78 received continuous subcutaneous abdominal injections of 2.4 mg of JY09 injection in the morning, once weekly (total of 8 administrations). All doses were to be administered within 3 min.

Treatment:

Drug: Digoxin tablet

Drug: Exendin-4 Fc fusion protein (JY09) injection

Drug: Metformin Hydrochloride tablet

Drug: Rosuvastatin calcium tablets